1. Field of Invention
The present invention relates to a method for preparation of N-methyl-3-(2-tributylstannylphenoxy)-3-phenylpropanamine (MSPP), and particularly to formation of a labeling precursor MSPP with a leaving group Bu3Sn.
2. Related Art
Norepinephrine, together with dopamine and serotonin are three important monoamine neurotransmitters in the brain, and are responsible for regulation of all mental and physical activities. For a long time, it is considered that norepinephrine and a uptake system are closely associated with treatment of neuropsychological disorders, for example, norepinephrine transporter (NET) and serotonin transporter are both useful as anti-depression therapeutic agents (A. Galli et al., J. Exp. Biol. 1995, 198: 2197-2212).
Where neurotransporter is imaged in combination with nuclear medicine imaging technology, both Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) can be used in research of treatment opportunities of anti-depression drugs, thus being beneficial to clinical treatment of diseases. At present, contrast media for serotonin include [123I]ADAM, [11C]MADAM, [11C]DASB, and [19F]-4-F-ADAM, and so on, but there are fewer contrast media for NET.
For development of nuclear medicine imaging technology of NET, nuclear pharmaceuticals capable of binding to NET need be found. Currently, the most commonly used nuclear pharmaceuticals capable of specifically binding to NET includes earlier desipramine and latter reboxetine and nisoxetine, in which a contrast medium with desipramine as a labeling is radioactive 11C labeled 11C-desipramine, and a contrast medium with reboxetine or a structural analogue thereof as a labeling precursor is 11C-MeNER. Considering that SPECT is one of most commonly used imaging modalities in diagnosis of diseases with nuclear pharmaceuticals at present, it is necessary to develop nuclear pharmaceuticals useful in a SPECT system.
(R)—N-methyl-3-(2-iodophenoxy)-3-phenylpropanamine (MIPP) is obtained by iodinating at Position 2 of a phenyl ring in nisoxetine, and has the chemical structure below:

which is useful as a contrast medium for NET. In 2004, Y. Kiyono suggested in a research that (R)—[123I]MIPP has strong selective affinity for NET in brain; moreover, lipophilic property of MIPP enables MIPP to penetrate the blood brain barrier and enter the brain, and thus MIPP is useful as a contrast medium for norepinephrine in brain central nervous system, and is beneficial to research and diagnosis of neuropsychological disorders such as depression (Y. Kiyono et al., Nucl. Med. Biol. 2004, 31:147-153).
The scheme for preparing (R)—[123I]MIPP is as follows.

(R)—N-methyl-3-(2-bromophenoxy)-3-phenylpropanamine ((R)-MBPP), as a labeling precursor (S. Chumpradit et al., J. Med. Chem. 1992, 35: 4492-4497), is subjected to solid-state halogen-exchange reaction with iodide ions at a high temperature of 140° C., and then the resulting product is purified through reverse-phase liquid chromatography (LC). As (R)—[123I]MIPP and (R)-MBPP have similar properties, purification is quite time consuming. Therefore, finding a precursor with physical and chemical properties different from those of contrast label (R)—[123I]MIPP can facilitate simplification of the preparation process and purification steps.